Bennett Charles L, Kim Benjamin, Zakarija Anaadriana, Bandarenko Nicholas, Pandey Dilip K, Buffie Charlie G, McKoy June M, Tevar Amul D, Cursio John F, Yarnold Paul R, Kwaan Hau C, De Masi Davide, Sarode Ravindra, Raife Thomas J, Kiss Joseph E, Raisch Dennis W, Davidson Charles, Sadler J Evan, Ortel Thomas L, Zheng X Long, Kato Seiji, Matsumoto Masanori, Uemura Masahito, Fujimura Yoshihiro
VA Center for Management of Complex Chronic Care at Jesse Brown VA Medical Center, Division of Hematology/Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
J Am Coll Cardiol. 2007 Sep 18;50(12):1138-43. doi: 10.1016/j.jacc.2007.04.093. Epub 2007 Sep 4.
We sought to describe clinical and laboratory findings for a large cohort of patients with thienopyridine-associated thrombotic thrombocytopenic purpura (TTP).
The thienopyridine derivatives, ticlopidine and clopidogrel, are the 2 most common drugs associated with TTP in databases maintained by the U.S. Food and Drug Administration (FDA).
Clinical reports of TTP associated with clopidogrel and ticlopidine were identified from medical records, published case reports, and FDA case reports (n = 128). Duration of thienopyridine exposure, clinical and laboratory findings, and survival were recorded. ADAMTS13 activity (n = 39) and inhibitor (n = 30) were measured for a subset of individuals.
Compared with clopidogrel-associated TTP cases (n = 35), ticlopidine-associated TTP cases (n = 93) were more likely to have received more than 2 weeks of drug (90% vs. 26%), to be severely thrombocytopenic (84% vs. 60%), and to have normal renal function (72% vs. 45%) (p < 0.01 for each). Compared with TTP patients with ADAMTS13 activity >15% (n = 13), TTP patients with severely deficient ADAMTS13 activity (n = 26) were more likely to have received ticlopidine (92.3% vs. 46.2%, p < 0.003). Among patients who developed TTP >2 weeks after thienopyridine, therapeutic plasma exchange (TPE) increased likelihood of survival (84% vs. 38%, p < 0.05). Among patients who developed TTP within 2 weeks of starting thienopyridines, survival was 77% with TPE and 78% without.
Thrombotic thrombocytopenic purpura is a rare complication of thienopyridine treatment. This drug toxicity appears to occur by 2 different mechanistic pathways, characterized primarily by time of onset before versus after 2 weeks of thienopyridine administration. If TTP occurs after 2 weeks of ticlopidine or clopidogrel therapy, therapeutic plasma exchange must be promptly instituted to enhance likelihood of survival.
我们试图描述一大群噻吩并吡啶相关血栓性血小板减少性紫癜（TTP）患者的临床和实验室检查结果。
在美国食品药品监督管理局（FDA）维护的数据库中，噻吩并吡啶衍生物噻氯匹定和氯吡格雷是与TTP相关的两种最常见药物。
从医疗记录、已发表的病例报告和FDA病例报告中识别出与氯吡格雷和噻氯匹定相关的TTP临床报告（n = 128）。记录噻吩并吡啶暴露时间、临床和实验室检查结果以及生存率。对一部分个体测量ADAMTS13活性（n = 39）和抑制剂（n = 30）。
与氯吡格雷相关的TTP病例（n = 35）相比，噻氯匹定相关的TTP病例（n = 93）更有可能接受超过2周的药物治疗（90%对26%）、严重血小板减少（84%对60%）以及肾功能正常（72%对45%）（每项p < 0.01）。与ADAMTS13活性>15%的TTP患者（n = 13）相比，ADAMTS13活性严重缺乏的TTP患者（n = 26）更有可能接受噻氯匹定治疗（92.3%对46.2%，p < 0.003）。在噻吩并吡啶治疗2周后发生TTP的患者中，治疗性血浆置换（TPE）提高了生存率（84%对38%，p < 0.05）。在开始噻吩并吡啶治疗2周内发生TTP的患者中，接受TPE的生存率为77%，未接受TPE的生存率为78%。
血栓性血小板减少性紫癜是噻吩并吡啶治疗的一种罕见并发症。这种药物毒性似乎通过两种不同的机制途径发生，主要特征是噻吩并吡啶给药2周之前与之后的发病时间。如果在噻氯匹定或氯吡格雷治疗2周后发生TTP，必须立即进行治疗性血浆置换以提高生存率。
